Multimodal fast optical interrogation of neural circuitry
Multimodal fast optical interrogation of neural circuitry
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DOI：
10.1038/nature05744
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发表时间：
2007-04-05
期刊：
影响因子：
64.8
通讯作者：
Deisseroth, Karl
中科院分区：
文献类型：
--
作者：
Zhang, Feng;Wang, Li-Ping;Deisseroth, Karl
我们对行动、思维和情绪等系统级神经过程的细胞实现的理解受到了工具的限制，这些工具可以用来询问完好无损的活脑组织中的特定类别的神经细胞。在这里，我们发现并开发了一种古细菌光驱动氯化物泵(NpHR)，用于对神经活动进行时间上精确的光学抑制。NpHR可以敲除单个动作电位，也可以持续阻断尖峰电位。NpHR与我们之前描述的光激发技术ChR2兼容，因为两个相对的探测器工作在相似的光功率下，但具有良好分离的作用光谱。NpHR和ChR2一样，在没有外源性辅助因子的哺乳动物中发挥作用，这两个探针可以与哺乳动物脑组织中的钙成像相结合，进行双向光学调制和读出神经活动。同样，NpHR和ChR2可以共同靶向秀丽线虫的肌肉和胆碱能运动神经元来双向控制运动。NpHR和ChR2形成了一个完整的系统，用于对活的神经回路进行多模式、高速、基因靶向、全光询问。
Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.